Magnetic resonance tracking of transplanted neural stem cells labeled with superparamagnetic iron oxides in APP/PS1 transgenic mice / 中华放射学杂志

ABSTRACT

Objective To label neural stem cells (NSCs) with superparamagnetic iron oxides (SPIO) and to explore the tropism of NSCs after transplantation into the hippocampus of APP/PS1 AD mice by MRI.Methods NSCs from C57BL/6 mouse were cultured and identified.Feridex and Poly-L-Lysine were added into the medium to be co-cultured to make magnetic labeled NSCs and transmission electron microscopy was used to identify the iron particles in NSCs.Transgenic (tg) and wild-type (wt) mice at 12 months of age were divided into three groups SPIOs labeled NSCs group (A and C),unlabeled NSCs group(B).Feridex-labeled NSCs were migrated into the hippocampus of APP/PS1 AD mice to monitor in vivo by MRI.After 1,2,4 and 6 weeks,the mice were sacrificed and their brain tissues were sectioned to investigate the migration of SPIO labeled NSCs and compared with MRI.Results NSCs of C57BL/6 mice were cultured successfully.Transmission electron microscope showed visible iron granules in cytoplasm.MRI detection of labeled cells T2WI and T2* WI showed remarkable low signal intensity at the hippocampus injection points 1 week after transplantation,particularly on T2* WI.Area of low signal intensity enlarged increasingly along the injection points after 2 weeks.At 4 weeks,area of low signal intensity spread throughout the hippocampus,but intensity shadowed Six weeks later,low signal intensity almost disappeared.There was no obvious low signal change in unlabeled cell transplantation group.For wt mice,size and location of low signal did not appear obvious change at all designated time points.Prussian blue positive cells were observed in the hippocampus,indicating that NSCs labeled with SPIO could survive,migrate and differentiate in the brain of the APP/PS1 AD mice.Changes of pathology were well correlated with the area where a signal intensity loss was observed in MRI 1,2,4 and 6 weeks after transplantation Conclusions Diffuse migration of transplanted NSCs labeled with SPIO is observed in the hippocampus in APP/PS1 tg mice,and MRI technique is an ideal method for tracking labeled stem cells after grafting in vivo.